We plan to examine the mechanisms responsible for daily rhythms in the rates at which the mammalian pineal gland synthesizes the hormone melatonin, and at which the brain and sympathetically-innervated tissues synthesize the neurotransmitter norepinephrine. Pineal melatonin synthesis is controlled by environmental lighting acting indirectly, via the eyes and the sympathetic nerves. Studies will be done to define the action spectra of light waves capable of influencing the pineal, the gonads, and daily rhythms in neuroendocrine functions (e.g., in body temperature). Pineals maintained in organ culture synthesize C14- melatonin (and C14-protein) from C14-tryptophan; melatonin synthesis is enhanced by adding norepinephrine or dibutyryl cyclic AMP to the medium. This phenomenon will be used to examine the properties of norepinephrine receptors, the control of serotonin and melatonin synthesis, and the mechanisms of action of various psychotropic drugs. We will attempt to develop a method for estimating melatonin synthesis in man, and studies will be done to identify melatonin metabolites present in rat brain following intracisternal administration of the indole. The role of the pineal in annual gonadal rhythms will be examined in various species (sheep, seals, mink, ferets), as will the mechanisms by which melatonin acts on serotonin-containing neurons in the brain. The mechanisms which cause the brain to accumulate more H3-catecholamines at one time of day than at another will be studied, and these rhythms will be used as a model system for examining the control of brain catecholamine metabolism in general.